基于四氢吡啶并吲哚支架的前列腺素D2受体拮抗剂的鉴定
Identification of prostaglandin D2 receptor antagonists based on a tetrahydropyridoindole scaffold.
作者信息
Beaulieu Christian, Guay Daniel, Wang Zhaoyin, Leblanc Yves, Roy Patrick, Dufresne Claude, Zamboni Robert, Berthelette Carl, Day Stephen, Tsou Nancy, Denis Danielle, Greig Gillian, Mathieu Marie-Claude, O'Neill Gary
机构信息
Department of Medicinal Chemistry, Merck Frosst Canada & Co., 16711 Trans Canada Hwy, Kirkland, Que., Canada.
出版信息
Bioorg Med Chem Lett. 2008 Apr 15;18(8):2696-700. doi: 10.1016/j.bmcl.2008.03.015. Epub 2008 Mar 10.
A new series of indole-based antagonists of the PGD(2) receptor subtype 1 (DP1 receptor) was identified and the progress of the structure-activity relationship study to the identification of potent and selective antagonists is presented. Selective DP1 antagonists with high potency and selectivity were prepared. Of particular interest is the DP1 antagonist 26 with a K(i) value of 1 nM for the DP1 receptor and an IC(50) value of 4.6 nM in a DP1 functional assay for the inhibition of the PGD(2) induced cAMP production in platelet rich plasma (PRP).
鉴定出了一系列新型基于吲哚的前列腺素D2受体亚型1（DP1受体）拮抗剂，并介绍了结构-活性关系研究在鉴定强效和选择性拮抗剂方面的进展。制备了具有高效力和选择性的DP1拮抗剂。特别值得关注的是DP1拮抗剂26，其对DP1受体的K(i)值为1 nM，在DP1功能测定中，对富含血小板血浆（PRP）中PGD(2)诱导的环磷酸腺苷（cAMP）产生的抑制作用的IC(50)值为4.6 nM。
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